EP0063731B1 - Procédé pour la préparation d'acides carboxyliques optiquement actifs - Google Patents

Procédé pour la préparation d'acides carboxyliques optiquement actifs Download PDF

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Publication number
EP0063731B1
EP0063731B1 EP82103013A EP82103013A EP0063731B1 EP 0063731 B1 EP0063731 B1 EP 0063731B1 EP 82103013 A EP82103013 A EP 82103013A EP 82103013 A EP82103013 A EP 82103013A EP 0063731 B1 EP0063731 B1 EP 0063731B1
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EP
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Prior art keywords
optically active
alcohol
tertiary amine
acid
radicals
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EP82103013A
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German (de)
English (en)
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EP0063731A1 (fr
Inventor
Christoph Prof.Dr. Ruechardt
Joachim Jaehme
Ulrich Salz
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BASF SE
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BASF SE
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
    • C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/46—Preparation of carboxylic acid esters from ketenes or polyketenes

Definitions

  • the present invention relates to an improved process for the preparation of optically active carboxylic acids of the general formula I.
  • R 1 stands for an organic radical which is linked via a C atom to the asymmetric C ′ atom and in which R 2 denotes one of the radicals R 1 (but not the same radical), halogen or an organic radical, which is bound to the asymmetric C 'atom via an O atom.
  • the radicals R 2 are the radicals R 1 with the proviso that R 2 ⁇ R 1 , and moreover halogen such as fluorine, chlorine, bromine and iodine and organic radicals which have an oxygen atom attached to the prochiral carbon atom are bound.
  • Starting compounds II of the latter type thus have the general formula Ila in which the radical R 3 z. B. can be one of the radicals mentioned for R 1 .
  • the ketenes II are either known or can be obtained by known methods, preferably by reacting the corresponding carboxylic acid chlorides II 'with a tertiary amine
  • the tertiary amine III required for the reaction according to the invention can be any tertiary nitrogen base, that is, for. B. a trialkylamine with C 1 -C 2o alkyl radicals, such as trimethylamine, triethylamine, tributylamine and dimethylstearylamine, a cycloaliphatic amine such as N-methylpyrrolidine, N-methylpiperidine and N-methylmorpholine, an aromatic amine such as dimethylaniline, other a heterocyclic nitrogen base such as pyridine or Quinoline.
  • Polycyclic bridgehead amines such as 1,4-diazabicycio- [2.2.2] octane (“DABCO •) are particularly suitable.
  • the tertiary amine III need not be optically active as in the Pracejus process mentioned at the outset, but the optical yield can be increased in some cases if an optically active tertiary amine, e.g. B. uses an optically active 1,2-dimethylpiperidine or N, N-dimethyl-1-phenylethylamine. Which of the two enantiomers influences the reaction in the desired sense (the other can possibly impair it) can be determined by a simple preliminary experiment.
  • the reaction according to the invention is presumably via an intermediate of the type which provides the proton of the optically active alcohol IV with a preferred direction of entry into the molecule, it is advisable to use the tertiary amine III in sufficient amount so that this effect is not caused by a less specific addition of the alcohol, as occurs in the absence of the amine observe is superimposed.
  • 0.5-1 mol of the amine III per mol II is used, but often smaller amounts are also sufficient (down to about 0.1 mol). In some cases, a stoichiometric excess of the amine up to about 10 mol can be advantageous.
  • the process according to the invention is not based on the isolated ketenes II but leaves them in situ, e.g. B. from the carboxylic acid chlorides II ', preferably one uses the total amount of the amine required for both reaction steps, ie 1.1-10, preferably 1.5-2 mol per mol II'. Since a strongly basic amine is generally required for the formation of ketene, however, one is preferred for the step according to the invention, in which the N atom, as with (relatively weakly basic) pyridine or as with DABCO, is sterically hindered as little as possible, so it is often advisable also to use two different amines.
  • the type of alcohol IV if it is only optically active, has in principle no influence on the success of the method according to the previous observations.
  • the chirality center can basically be located anywhere on the molecule, the best are achieved Results with alcohols in which the hydroxyl group is located on a chiral carbon atom. It is also irrelevant whether the alcohol contains one or more chiral centers.
  • Suitable asymmetric alcohols are e.g. B. the optical isomers of iso- and heterocyclic 1-aryl-C 1 -C 4 -alkan-1-ols, the aryl group including C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups, halogen, nitro groups , Cyano groups, dialkylamino groups and alkylene amino groups such as the N-pyrrolidino and N-piperidino groups may be substituted.
  • Preferred aryl groups are the naphthyl group, the pyridyl group and especially the phenyl group.
  • the simplest and therefore often particularly preferred alcohol is 1-phenylethan-1-ol.
  • optically active terpene alcohols such as menthol and optically active amino alcohols IV 'such as N-methylephedrine (1-phenyl-2-dimethylaminopropan-1-ol) and 2-amino-butan-1-ol.
  • amino alcohols such as menthol and optically active amino alcohols IV '
  • N-methylephedrine (1-phenyl-2-dimethylaminopropan-1-ol) and 2-amino-butan-1-ol.
  • Alcohol IV is used at least in a stoichiometric, but preferably in excess (up to about 10 mol) amount to ketene II.
  • the reaction is carried out like a conventional alcohol addition to ketenes.
  • a range of (- 80) - 100 ° C is recommended for the reaction temperatures, whereby the stereospecific selectivity normally decreases with increasing temperature.
  • Suitable solvents are aprotic liquids such as benzene, toluene, C 4 -C 8 -alkanes, cyclohexane, ethers such as dimethyl and diethyl ether and cyclic ethers such as dioxane and tetrahydrofuran and haloalkanes such as methylene chloride. It is preferable to work in a 1-20% solution.
  • the reaction mixture is worked up in the customary manner by removing the solvent, the excess amine III and the excess alcohol from the ester I 'formed
  • R 4 residue of the alcohol R 4 0H (IV) is distilled off, a fractionation of these components, if they are to be reused for a further reaction batch, not necessary. If one started from carboxylic acid chloride II ', the ammonium chloride R 3 N ⁇ HCl, which is usually obtained in crystalline form, is separated off before further work-up.
  • ester I is then in the usual way - z. B. with dilute hydrochloric acid or with dilute sodium hydroxide solution at 30-100 ° C in the acid I or the Na salt of the acid on the one hand and the alcohol IV, after which the alcohol can be recycled back into the reaction.
  • the acid is isolated as usual and, if desired, purified.
  • the process according to the invention ultimately consists in a (prochiral) ketene II or its precursor, a racemic carboxylic acid chloride II ', in a high optical yield in an optically active carboxylic acid I convict. It is advantageous here that the method is obviously particularly well suited for continuous operation.
  • optical yields of at least 30, but mostly 70-80% can be achieved. It cannot be reliably predicted which of the two isomers, whether the R or the S isomer is formed in excess, but the R / S ratio is reversed when the antipodal alcohol is used.
  • Process products I are either themselves important active ingredients or intermediates for the production of physiologically active substances. As easily accessible optically active acids, they in turn also serve to separate racemic alcohols or amines via diastereomeric pairs of compounds.
  • This mixture was then quickly mixed with a solution of 0.8 g (10 mmol) of pyridine and 1.6 g (10 mmol) of 1-menthol (2-isopropyl-5-methyl-cyclohexanol) at 0 ° C. and then 3 h at 0 ° C. The mixture was then stirred at 50 ° C. for 12 hours with 50 ml of concentrated hydrochloric acid, after which the aqueous phase was separated off and the organic phase was worked up as usual for the hydratropic acid.
  • This acid was prepared analogously to Example 1 from R, S-2-phenoxypropionyl chloride, triethylamine, pyridine and S-1-phenylethanol in an optical yield of 28% corresponding to an enantiomer ratio of 64:36.
  • the optical yield of the S-hydratropic acid was 60%.
  • DABCO 1,4-diazabicyclo [2,2,2] octane
  • This compound was prepared analogously to Example 5 from 2-chlorophenyl acetylchloride and 1-phenylethanol and with diethyl ether as solvent in an optical yield of 47%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Claims (4)

1. Procédé de préparation d'acides carboxyliques optiquement actifs de la formule générale I
Figure imgb0014
dans laquelle R1 représente un reste organique, relié par un atome de carbone à l'atome de carbone asymétrique C', et R2 possède la même signification que R1, sans lui être identique, ou représente un atome d'halogène ou un reste organique, relié par un atome d'oxygène à l'atome de carbone asymétrique C', par réaction d'un cétène Il
Figure imgb0015
en phase liquide homogène et en présence d'une amine tertiaire III avec un alcool, suivie de la transformation de l'ester formé en acide, caractérisé en ce que l'alcool employé est un alcool optiquement actif IV.
2. Variante du procédé suivant la revendication 1, caractérisée en ce que l'amine tertiaire III et l'alcool optiquement actif IV sont remplacés par un tert.-amino-alcool. IV' optiquement actif.
3. Procédé suivant les revendications 1 et 2, caractérisé en ce que l'on utilise la solution d'un cétène II, préparé in situ à partir d'un chlorure d'acide carboxylique II'
Figure imgb0016
et d'une amine tertiaire.
4. Procédé suivant la revendication 1, caractérisé en ce que l'amine tertiaire mise en oeuvre est une amine tertiaire optiquement active.
EP82103013A 1981-04-25 1982-04-08 Procédé pour la préparation d'acides carboxyliques optiquement actifs Expired EP0063731B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT82103013T ATE8243T1 (de) 1981-04-25 1982-04-08 Verfahren zur herstellung von optisch aktiven carbonsaeuren.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19813116474 DE3116474A1 (de) 1981-04-25 1981-04-25 Verfahren zur herstellung von optisch aktiven carbonsaeuren
DE3116474 1981-04-25

Publications (2)

Publication Number Publication Date
EP0063731A1 EP0063731A1 (fr) 1982-11-03
EP0063731B1 true EP0063731B1 (fr) 1984-07-04

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP82103013A Expired EP0063731B1 (fr) 1981-04-25 1982-04-08 Procédé pour la préparation d'acides carboxyliques optiquement actifs

Country Status (8)

Country Link
US (1) US4691020A (fr)
EP (1) EP0063731B1 (fr)
JP (1) JPS57181021A (fr)
AT (1) ATE8243T1 (fr)
CA (1) CA1181766A (fr)
DE (2) DE3116474A1 (fr)
ES (1) ES8307704A1 (fr)
HU (1) HU186861B (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ206106A (en) * 1982-11-22 1987-10-30 Shell Oil Co Processes for the preparation of optically active cyanomethyl esters of alpha-chiral carboxylic acids and optionally substituted s-alpha-cyano-3-phenoxybenzyl alcohol
EP0291626A3 (fr) * 1982-11-22 1989-05-31 E.I. Du Pont De Nemours And Company Procédé pour la préparation d'esters cyanométhyliques optiquement actifs
US4546198A (en) * 1983-01-18 1985-10-08 Shell Oil Company Asymmetric synthesis of esters and acids
US4529810A (en) * 1983-02-22 1985-07-16 Shell Oil Company Preparation of optically-active alpha-substituted carboxylic esters and acids
US4709082A (en) * 1984-10-25 1987-11-24 Nissan Chemical Industries, Ltd. 2-phenylpropionic acid esters, method for optical resolution thereof and optically active substance thereof
JPS61126035A (ja) * 1985-06-05 1986-06-13 Daicel Chem Ind Ltd 光学分割方法
GB8514489D0 (en) * 1985-06-07 1985-07-10 Shell Int Research Producing 2-arylpropionic acids
JPS62175446A (ja) * 1986-01-27 1987-08-01 Daicel Chem Ind Ltd （±）−１−（１−ナフチル）エチルアミンの光学分割法
US4940813A (en) * 1989-03-31 1990-07-10 Merck & Co., Inc. Resolution of a carboxylic acid
DE19815833A1 (de) * 1998-04-09 1999-10-14 Basf Ag Verfahren zur Herstellung von Linalylacetat

Also Published As

Publication number Publication date
EP0063731A1 (fr) 1982-11-03
JPS57181021A (en) 1982-11-08
ATE8243T1 (de) 1984-07-15
CA1181766A (fr) 1985-01-29
ES511651A0 (es) 1983-08-16
ES8307704A1 (es) 1983-08-16
HU186861B (en) 1985-10-28
DE3116474A1 (de) 1982-11-11
US4691020A (en) 1987-09-01
DE3260326D1 (en) 1984-08-09

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